Type 1 diabetes (also known as type 1 diabetes mellitus), which generally develops in children, is a serious chronic disease with an unknown cause. It is characterized by autoimmune destruction of insulin-producing (beta) β-cells in the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. Globally, type 1 diabetes affects between 15 and 30 million people worldwide (World Health Organization). The incidence of childhood onset diabetes is increasing in many countries (Patterson et al., Diabetes Res. Clin. Pract., 2014, 103: 161-175; Tamayo et al., Diabetes Res. Clin. Pract., 2014, 103: 206-217), with an estimated 80,000 children developing the disease each year. Insulin therapy, which is essential for survival of type 1 diabetes patients, must be continued indefinitely and includes multiple daily injections. In addition to insulin therapy, dietary management is important. Untreated or poorly managed diabetes can cause many complications, including serious long-term complications, which include heart disease, stroke, kidney failure, foot ulcers, damage to the eyes, and coma. In some type 1 diabetics (such as patients with brittle type 1 diabetes—a severe instability of blood glucose levels, which results in disruption of life and often recurrent and/or prolonged hospitalization), complications may also arise from low blood sugar caused by excessive treatment.
One alternative treatment approach to insulin injection is the subcutaneous implantation of insulin pumps. Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion (Deiss et al., Diabetes Care, 2006, 29: 2730-2732; O'Connell et al., Diabetologia, 2009, 52: 1250-1257; Raccah et al., Diabetes Diabetes Care, 2009, 32: 2245-2250; Battelino et al., Diabetologia, 2012, 55: 3155-3162). Despite frequent use in large diabetes centers, continuous glucose monitoring is not commonly employed for pediatric patients (Klonoff et al., J. Clin. Endocrinol. Metab., 2011, 96: 2968-2979; Phillip et al., Pediatr. Diabetes, 2012, 13: 215-228). One reason for this is the lack of infrastructure and personnel qualified to teach patients and their families to use this technology effectively (Tumminia et al., Patient Prefer Adherence, 2015, 9: 1263-1270; Joshi et al., Curr. Diab. Rep., 2015, 15: 81). To lighten the burden of type 1 diabetes for patients and their families, steady progress is being made toward the development of a so-called “artificial pancreas”, which may ultimately be a fully automated, closed-loop insulin delivery system combining continuous glucose sensor with insulin infusion pump (or insulin patch pump) using validated mathematical algorithms to drive the continuous insulin infusion (systems developed for example by Medtronic, Abbott, Dexcom, etc. . . . )
Another alternative to exogenous insulin is allotransplantation of pancreatic islets. The Edmonton Protocol has demonstrated the feasibility and success of islet transplantation to restore euglycemia in patients (Shapiro et al., N. Engl. J. Med., 2000, 343: 230-238). However, this procedure, which attempts to replenish the depleted β-cell reserve, is limited by the shortage of human organs of sufficient quality, the need for multiple donors per patient, inconsistent islet yields, the need for immunosuppressive therapy and the resulting deleterious side effects. The minimally invasive subcutaneous transplantation of encapsulated pig or allogenic islets without immunosuppression appears today as a mature therapy (Dufrane et al., Transplantation, 2006, 81: 1345-1353; Elliott et al., Xenotransplantation, 2007, 14: 157-161; Zimmermann et al., Curr. Diab. Rep., 2007, 7: 314-320; Dufrane et al., World J. Gastroenterol., 2012, 18: 6885-6893; Sakata et al., World J. Gastroenterol., 2012, 3: 19-26; O'Sullivan et al., Endocr. Rev., 2011, 32: 827-844; Ramesh et al., Curr. Diabetes Rev., 2013, 9: 294-311; Sharp et al., Adv. Drug Deliv. Rev., 2014, 67-68: 35-73; Zhu et al., Front Surg., 2014, 1: 7; Zhu et al., J. Zhejiang Univ. Sci. B, 2015, 16: 329-343). In encapsulation, cells are encased within a biocompatible matrix, whose primary role is to create, besides an extracellular matrix, a barrier against immune cells and cytotoxic molecules, thus avoiding rejection while still allowing the active diffusion of oxygen, micro- and macro-nutrients, and hormones. However, some last obstacles persist impeding an optimal and durable efficiency this cell therapy. In particular, alginate, which is the standard polymer for islet encapsulation, has several drawbacks: it is difficult to purify and sterilize, it can be immunogenic, it forms hydrogels that are unstable, reversible, that can dissociate and that requires an invasive implantation. Invasive implantations involve an act of surgery which, in addition to common surgical complications, increases the inflammatory response and the risk of rejection.
Thus, there still remains, in the art, an ongoing need for new strategies that can fulfill the promise of establishing islet transplantation as a simple, safe and successful type 1 diabetes therapy.